ANALYSIS OF LIPOLYTIC TRAFFICKING IN FAT AND MUSCLE

脂肪和肌肉中的脂解贩运分析

• 批准号: 8361937
• 负责人: James G Granneman
• 金额: $ 2.47万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361937
• 关键词: Atherosclerosis; Binding; Cardiomyopathies; Cell physiology; Data; Diabetes Mellitus; Disease; Fatty Acids; Fatty acid glycerol esters; Funding; Goals; Grant; Image Analysis; Knowledge; Lead; Lipase; Lipid Mobilization; Lipids; Lipolysis; Molecular; Muscle; National Center for Research Resources; Organelles; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Role; Scaffolding Protein; Source; Structure; Surface; Techniques; Triglycerides; United States National Institutes of Health; cost; obesity treatment; perilipin; protein transport; small molecule; trafficking

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The storage and mobilization of lipid are fundamental cellular processes, and its dysregulation contributes to numerous diseases including diabetes, atherosclerosis and cardiomyopathy. Our central hypothesis is that regulated lipolysis involves the orderly trafficking of lipases and co-activators to specialized lipid droplet structures that are organized by specific lipid droplet scaffold proteins. We anticipate that knowledge of the specific molecular interactions that control ectopic lipid clearance will allow us to devise screens for small molecules that promote this activity, with the long term goal of identifying lead compounds for treatment of obesity-related lipotoxicity. Our lab is investigating cellular and molecular mechanisms of lipolysis in fat and muscle. We and others have shown that that mobilization of fatty acids from stored triglyceride involves specific trafficking of proteins to the droplet surface. There are direct data demonstrating the central role of PAT proteins (perilipin/ADRP/TIP47) in organizing lipolytic protein trafficking and indirect data that indicating that this occurs on specialized lipid droplets or domains of large lipid droplets. Furthermore, in addition to protein trafficking, activation of lipolysis appears to involve structural changes in the droplet surface, such as microdroplet formation. We believe that application of the 3D SEM and TEM techniques developed by NCMIR would allow unprecedented analysis if this dynamic and important organelle.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 脂质的储存和动员是基本的细胞过程，其功能失调会导致包括糖尿病，动脉粥样硬化和心肌病在内的许多疾病。 我们的中心假设是，受调节的脂解涉及将脂肪酶和共激活因子的有序运输到由特定脂质液滴支架蛋白组织的专用脂质液滴结构上。我们预计，控制异位脂质清除率的特定分子相互作用的知识将使我们能够为促进这种活性的小分子设计筛选，其长期目标是鉴定铅化合物以治疗肥胖相关的脂肪毒性。 我们的实验室正在研究脂肪和肌肉中脂解的细胞和分子机制。 我们和其他人表明，从储存的甘油三酸酯中动员脂肪酸涉及将蛋白质的特定运输到液滴表面。 有直接的数据表明，PAT蛋白（Perilipin/ADRP/TIP47）在组织脂解蛋白运输和间接数据中的核心作用，这表明这发生在专用的脂质液滴或大脂肪液滴的域上。 此外，除了蛋白质运输外，脂解的激活似乎还涉及液滴表面的结构变化，例如微螺旋形成。我们认为，如果这种动态和重要的细胞器，NCMIR开发的3D SEM和TEM技术的应用将允许前所未有的分析。